Molecular structure of the cyanobacterial tumor‐promoting microcystins

FEBS Letters

Mierke, Dale F.²  Rudolph-Böhner, Sabine¹  Moroder, Luis¹ 

[1]Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, 82152 Martinsried, Germany

[2]Gustaf H. Carlson School of Chemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA

关键词: Microcystin;    Three-dimensional structure;    NMR;    Distance geometry;    Structure—function relationship;    The two variable l-amino acids present in the microcystin sequences are used to specify the toxins by single capital letter codes [15];   

DOI  :  10.1016/0014-5793(94)00680-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The three-dimensional structure of the two hepatotoxic microcystins LR and LY has been determined by two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy and distance geometry calculations. For the microcystin LY a single family of highly convergent structures was obtained. This family is characterized by a relatively compact boat-like ring structure with the large side chain of the Adda residue protruding from the concave side, in close proximity to the Tyr side chain. Conversely, for the microcystin LR the calculations result in three conformational families characterized by an even more compact ring structure. The Adda and Arg side chains protrude from the ring distal from one another caused by the repulsion between the guanido function of Arg and the hydrophobic Adda. The lower toxicity of the LY microcystin could result from the restricted access of the Adda side chain, an essential residue for activity, which results from the close proximity of the aromatic Tyr residue. A significant enthalpic cost would be expected for disturbance of this hydrophobic collapse and correspondingly lower binding affinity to receptor molecules would be predicted. From the structures of the two related microcystins, and homology with other known toxins, we propose a working hypothesis of the Adda side chain interacting with a hydrophobic pore of the phosphatases while the rest of the microcystin acts as a scaffold to help stabilize the interdigitation of the Adda with additional intermolecular interactions.

【 授权许可】

Unknown